- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01026246
EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-immune Adults
March 28, 2013 updated by: National Institute of Allergy and Infectious Diseases (NIAID)
Phase I, Double-Blinded, Placebo-Controlled Dosage-Escalation Study of the Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-immune Adults
Malaria is caused by a germ that people get from the bites of some mosquitoes.
It kills over 2 million people each year.
Many of the drugs used to treat malaria do not work as well as they used to and researchers are exploring other vaccines to prevent malaria.
The purpose of this study is to learn if the vaccine, called EBA-175 RII-NG, is safe and if it strengthens the body's defenses against malaria.
Participants will include 60 healthy adults, ages 18-40, recruited from Accra, Ghana.
Several dosages of the vaccine will be tested for safety.
The lowest dosages of the vaccine will be tested before the next higher dose is tested.
There will be two groups for each dose, one group will receive the vaccine and the other group will receive a placebo (salt water solution).
Participants may be involved in study related procedures for up to 398 days.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Malaria accounts for 500 million febrile illnesses and more than a million deaths annually.
The disease burden is heaviest in economically developing countries where it is estimated that up to 5 percent of the gross domestic product of sub-Saharan countries is consumed by the direct and indirect health costs of malaria.
Researchers propose to conduct a Phase I dosage-escalating study to assess the safety and immunogenicity of 3 different dosages of erythrocyte-binding antigen 175 kDA region II-nonglycosylated (EBA-175 RII-NG) recombinant Plasmodium falciparum (Pf) vaccine adjuvanted with Adju-Phos (aluminum phosphate adjuvant): 5, 20, and 80 micrograms (mcg), given in 3 doses at 0, 1, and 6 months by intramuscular (IM) injection to healthy young adults in a malaria endemic area (semi-immune adults).
One dose of vaccine will be given at each time point.
The primary objective is to assess the safety and reactogenicity (tolerability) of ascending dosages of EBA-175 RII-NG vaccine among healthy subjects given in 3 IM doses at 0, 1 and 6 months.
The secondary objective is to evaluate the immunogenicity of the EBA-175 RII-NG vaccine by measuring anti-EBA-175 RII-NG antibodies using enzyme-linked immunosorbent assay (ELISA), inhibition of Plasmodium falciparum growth in vitro, and inhibition of binding of EBA-175 RII-NG to red blood cells (RBCs).
Participants will include 60 malaria semi-immune healthy subjects between the ages of 18 and 40 years, males and females, recruited from Accra, Ghana.
Subjects will be randomized to receive 3 doses of the vaccine or saline placebo by the intramuscular route in a 9:1 ratio at 0, 1 and 6 months.
The safety and immunogenicity of ascending dosages of the vaccine will be assessed.
Eighteen subjects will receive vaccine at each of the following dosage levels: 5, 20, and 80 mcg.
Two subjects will receive placebo for each dosage level.
Dosage escalation will proceed only after review of the 2-week safety data of the 2 initial doses of the prior dosage level.
Study Type
Interventional
Enrollment (Actual)
60
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Greater Accra
-
Legon, Greater Accra, Ghana
- Noguchi Memorial Institute for Medical Research - Immunology
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 40 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy males and healthy non-pregnant and non breastfeeding females between the ages of 18 and 40 years.
- Females of childbearing potential must agree to practice adequate contraception through out the study and for 3 months after the third vaccination (including abstinence; hormonal contraception; condoms with spermicidal agents); males with female partners of childbearing age must agree to use condoms or other birth control.
- Good health as determined by screening medical history, physical examination (PE), and routine laboratory assessments.
- Willingness to comply with protocol requirements.
- Ability to provide informed consent before any protocol procedures are performed.
- Availability for follow-up for 12 months after the first immunization dose.
Exclusion Criteria:
- Regular use of medications other than vitamins and contraceptives.
- Current or recent (within the last 4 weeks prior to vaccination) treatment with parenteral, inhaled, or oral corticosteroids (intranasal steroids are acceptable), or other immunosuppressive agents, or chemotherapy.
- History of splenectomy.
- Abnormal screening laboratory values. Any abnormal screening value for any screening test, will exclude the subject from the study. An exception to this rule is the glucose measurement. Random plasma glucose will be measured on all subjects during the screening visit. Values higher than 110 mg/dl will be confirmed by a repeat fasting glucose measurement.
- History of or current medical, occupational, social or family problems as a result of alcohol or illicit drug use by the volunteer.
- History of moderate to severe mental illness, as defined by symptoms interfering with social or occupational function or suicidal thoughts/attempts.
- History of receiving blood or blood products (such as blood transfusion, platelet transfusion, immunoglobulins, hyperimmune serum) in the previous 6 months.
- Vaccination with a live vaccine within the past 30 days or with a non-replicating, inactivated, or subunit vaccine within the last 14 days.
- Known hypersensitivity to components of the vaccine [Erythrocyte-Binding Antigen 175 kDa Region II-Nonglycosylated (EBA-175 RII-NG), sucrose, or aluminum adjuvant].
- History of acute or chronic medical conditions including, but not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic and autoimmune/inflammatory conditions, sickle cell disease.
- History of anaphylaxis or severe hypersensitivity reaction.
- Severe asthma, as defined by an emergency room visit or hospitalization within the last 12 months.
- Pregnant or breastfeeding women, or women unwilling to use effective contraception during the study period.
- Acute illness, including temperature > 37.8 degrees Celsius within one week prior to vaccination.
- Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg).
- Concurrent participation in other investigational protocols or receipt of an investigational product within the previous 30 days.
- Identification of any condition that, in the opinion of the investigator, would affect the ability of the subject to understand or comply with the study protocol or would jeopardize the safety or rights of a subject participating in the study.
- History of malignancy, including hematologic and skin cancers, or known immunodeficiency syndrome.
- Pre-medication with analgesic or antipyretic in the 6 hours prior to vaccination, or planned medication with analgesic or antipyretic in the 24 hours following vaccination. This criterion should not preclude subjects receiving such medication after vaccination if the need arises.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group B: 20 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant
18 subjects to receive 20 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; 2 subjects to receive placebo.
|
The placebo used will be normal saline (0.9 percent NaCl).
EBA-175 RII-NG malaria vaccine is supplied as a white, translucent, cloudy, nonparticulate liquid suspension in single-dose clear glass vials pre-mixed with Adju-Phos aluminum phosphate adjuvant.
Each 2-mL vial of EBA-175 RII-NG vaccine contains: 0.7 mL (0.5 mL per dose) EBA-175 RII-NG, at the required dose concentration, 5 percent sucrose, 1.0 mg/mL (0.5 mg/0.5 mL per dose) aluminum as aluminum phosphate adjuvant, sodium phosphate buffer (10 mM sodium phosphate and 150 mM sodium chloride), and no preservative.
|
Experimental: Group A: 5 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant
18 subjects to receive 5 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; 2 subjects to receive placebo.
|
The placebo used will be normal saline (0.9 percent NaCl).
EBA-175 RII-NG malaria vaccine is supplied as a white, translucent, cloudy, nonparticulate liquid suspension in single-dose clear glass vials pre-mixed with Adju-Phos aluminum phosphate adjuvant.
Each 2-mL vial of EBA-175 RII-NG vaccine contains: 0.7 mL (0.5 mL per dose) EBA-175 RII-NG, at the required dose concentration, 5 percent sucrose, 1.0 mg/mL (0.5 mg/0.5 mL per dose) aluminum as aluminum phosphate adjuvant, sodium phosphate buffer (10 mM sodium phosphate and 150 mM sodium chloride), and no preservative.
|
Experimental: Group C: 80 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant
18 subjects to receive 80 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; 2 subjects to receive placebo.
|
The placebo used will be normal saline (0.9 percent NaCl).
EBA-175 RII-NG malaria vaccine is supplied as a white, translucent, cloudy, nonparticulate liquid suspension in single-dose clear glass vials pre-mixed with Adju-Phos aluminum phosphate adjuvant.
Each 2-mL vial of EBA-175 RII-NG vaccine contains: 0.7 mL (0.5 mL per dose) EBA-175 RII-NG, at the required dose concentration, 5 percent sucrose, 1.0 mg/mL (0.5 mg/0.5 mL per dose) aluminum as aluminum phosphate adjuvant, sodium phosphate buffer (10 mM sodium phosphate and 150 mM sodium chloride), and no preservative.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of subjects experiencing severe (Grade 3) solicited injection site reactions.
Time Frame: Within 14 days following vaccination.
|
Within 14 days following vaccination.
|
Number of subjects experiencing severe solicited systemic reactions (Grade 3).
Time Frame: Within 14 days following vaccination.
|
Within 14 days following vaccination.
|
Number of subjects experiencing severe (Grade 3) clinical laboratory values.
Time Frame: Within 14 days following vaccination.
|
Within 14 days following vaccination.
|
Number of subjects spontaneously reporting adverse events considered associated with the vaccination that are severe (Grade 3).
Time Frame: Duration of study.
|
Duration of study.
|
Serious adverse events considered associated with the vaccination.
Time Frame: Duration of study.
|
Duration of study.
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of subjects experiencing a 4-fold increase in Anti-EBA-175 RII-NG antibody level (ELISA).
Time Frame: Days 14, 28, 42, 180 and 194 relative to baseline.
|
Days 14, 28, 42, 180 and 194 relative to baseline.
|
Relative binding inhibition of recombinant EBA-175 RII-NG to human red blood cells in vitro in the presence of serum from immunized individuals.
Time Frame: Days 0, 14, 28, 42, 180 and 194.
|
Days 0, 14, 28, 42, 180 and 194.
|
Anti-EBA-175 RII-NG antibody level by enzyme-linked immunosorbent assay (ELISA).
Time Frame: Days 0, 14, 28, 42, 180 and 194.
|
Days 0, 14, 28, 42, 180 and 194.
|
Relative growth inhibition of Plasmodium falciparum in human red blood cells cultured in vitro in the presence of serum from immunized individuals.
Time Frame: Days 0, 14, 28, 42, 180 and 194.
|
Days 0, 14, 28, 42, 180 and 194.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2010
Primary Completion (Actual)
March 1, 2012
Study Completion (Actual)
March 1, 2012
Study Registration Dates
First Submitted
December 3, 2009
First Submitted That Met QC Criteria
December 3, 2009
First Posted (Estimate)
December 4, 2009
Study Record Updates
Last Update Posted (Estimate)
March 29, 2013
Last Update Submitted That Met QC Criteria
March 28, 2013
Last Verified
May 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 08-0009
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Plasmodium Falciparum Malaria
-
SanofiMedicines for Malaria VentureCompletedPlasmodium Falciparum InfectionBenin, Burkina Faso, Gabon, Kenya, Uganda
-
SanofiMedicines for Malaria VentureTerminatedPlasmodium Falciparum InfectionBenin, Burkina Faso, Gabon, Kenya, Mozambique, Uganda, Vietnam
-
Novartis PharmaceuticalsRecruitingUncomplicated Plasmodium Falciparum MalariaCôte D'Ivoire, Kenya, Ghana, Uganda
-
Medicines for Malaria VentureCompletedUncomplicated Plasmodium Falciparum MalariaUganda, Benin, Burkina Faso, Congo, The Democratic Republic of the, Gabon, Mozambique, Vietnam
-
Karolinska University HospitalMuhimbili University of Health and Allied SciencesCompletedUncomplicated Plasmodium Falciparum MalariaTanzania
-
Syamsudin Abdillah,Ph.D, Pharm DApt. Dian Yudianto; Dr. dr Erni J. Nelwan, Sp.PD, Ph.D; Apt.Hesty Utami Ramadaniati...CompletedUncomplicated Plasmodium FalciparumIndonesia
-
University of OxfordEuropean and Developing Countries Clinical Trials Partnership (EDCTP); Medical...RecruitingMalaria, Plasmodium FalciparumGambia
-
PfizerCompletedPLASMODIUM FALCIPARUM MALARIAIndia
-
Muhimbili University of Health and Allied SciencesUppsala University; The Swedish Research CouncilNot yet recruitingUncomplicated Plasmodium Falciparum MalariaTanzania
-
Novartis PharmaceuticalsEuropean and Developing Countries Clinical Trials Partnership (EDCTP)RecruitingUncomplicated Plasmodium Falciparum MalariaBurkina Faso, Mali, Gabon
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States